title: Valproic acid promotes human hair growth in in vitro culture model.
abstract: BACKGROUND
  β-Catenin, the transducer of Wnt signaling, is critical for the development and growth of hair follicles. In the absence of Wnt signals, cytoplasmic β-catenin is phosphorylated by glycogen synthase kinase (GSK)-3 and then degraded. Therefore, inhibition of GSK-3 may enhance hair growth via β-catenin stabilization. Valproic acid is an anticonvulsant and a mood-stabilizing drug that has been used for decades. Recently, valproic acid was reported to inhibit GSK-3β in neuronal cells, but its effect on human hair follicles remains unknown.
  
  
  OBJECTIVE
  To determine the effect of VPA on human hair growth.
  
  
  METHODS
  We investigated the effect of VPA on cultured human dermal papilla cells and outer root sheath cells and on an in vitro culture of human hair follicles, which were obtained from scalp skin samples of healthy volunteers. Anagen induction by valproic acid was evaluated using C57BL/6 mice model.
  
  
  RESULTS
  Valproic acid not only enhanced the viability of human dermal papilla cells and outer root sheath cells but also promoted elongation of the hair shaft and reduced catagen transition of human hair follicles in organ culture model. Valproic acid treatment of human dermal papilla cells led to increased β-catenin levels and nuclear accumulation and inhibition of GSK-3β by phosphorylation. In addition, valproic acid treatment accelerated the induction of anagen hair in 7-week-old female C57BL/6 mice.
  
  
  CONCLUSIONS
  Valproic acid enhanced human hair growth by increasing β-catenin and therefore may serve as an alternative therapeutic option for alopecia.
authors.affiliation: Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea; Institute of Human-Environment Interface Biology, Seoul National University, Seoul, Republic of Korea; Laboratory of Cutaneous Aging and Hair Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Seong Jin
authors.initials: SJ
authors.lastname: Jo
authors.forename: Soon-Jin
authors.initials: SJ
authors.lastname: Choi
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Yoon
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Lee
authors.forename: Won-Seok
authors.initials: WS
authors.lastname: Park
authors.forename: Phil-June
authors.initials: PJ
authors.lastname: Park
authors.forename: Kyu Han
authors.initials: KH
authors.lastname: Kim
authors.forename: Hee Chul
authors.initials: HC
authors.lastname: Eun
authors.forename: Ohsang
authors.initials: O
authors.lastname: Kwon
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D060466:Axin Protein / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006197:Hair / Q000187:drug effects* / Q000254:growth & development*; D018859:Hair Follicle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D046509:Tissue Culture Techniques; D014635:Valproic Acid / Q000494:pharmacology*; D051176:beta Catenin / Q000378:metabolism
chemical_list: C491761:AXIN2 protein, human; D060466:Axin Protein; C495270:CTNNB1 protein, human; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D051176:beta Catenin; C012589:trichostatin A; D014635:Valproic Acid; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; D000469:Alkaline Phosphatase
keywords: Dermal papilla; GSK-3 β; Hair; Valproic acid; β-catenin